CBY1 contains both NLS and NES sequences and continuously shuttles between the cytoplasm and the nucleus. Treatment of cells with leptomycin B (LMB), an inhibitor of XPO1-mediated nuclear export, results in nuclear accumulation of both CBY1 and 14-3-3/YWHAZ proteins (Li et al, 2008; Li et al, 2010). Consistent with this, CBY1 binds to XPO1 in an NES-dependent manner. 14-3-3/YWHAZ enhances the CBY1-XPO1 interaction, possibly by inducing a conformational change that exposes the adjacent NES sequence. Binding of 14-3-3/YWHAZ also inhibits the interaction of CBY1 with alpha-importin, additionally favouring its cytoplasmic localization. CBY1 NES mutants that are incapable of nuclear export show reduced ability to repress a beta-catenin-dependent reporter, and knockdown of endogenous CBY1 causes an accumulation of beta-catenin in the nucleus. These data support a role for CBY1 in the nuclear export of beta-catenin (Li et al, 2010). Despite growing evidence for a role for CBY1 in regulating WNT signaling, a formal requirement for CBY1 in vivo is still lacking.